This study aims to discuss MRI-guided cryoablation (CA) of in-transit (IT) metastases from melanoma and to retrospectively present our preliminary experience in such a specific field. Three female patients (mean age 55.6 years; range 39-64) were included, and eight IT metastases (mean size 12.4 ± 6.5 mm, range: 5-25) were treated in three different sessions. Technical success was 100%; and mean procedural time 129.3 ± 103 min. (range 42-243). Primary local tumour control was 100% at 1-, 6- and 12-month follow-up; and 87.5% at 18-month follow-up. Two complications were recorded (one minor and one major). MRI-guided CA is a novel therapy, which may be included in the armamentarium of local therapies of IT metastases.